The present research is directed to the problem of defining the ways in which membrane lipids influence the activities of membrane-bound enzymes. The kinetic and regulatory properties of UDP-glucuronyltransferase and glucose-6-phosphatase will be studied as a function of changing, through dietary manipulation, the fatty acid and phospholipid headgroup composition of microsomal membranes in order to determine the extent to which the activities of these enzymes can be modulated in vivo with these techniques. The effects of drugs which are known inducers of microsomal enzymes also will be studied in, in vivo and in vitro systems. Also, because Gunn rats have a genetically determined defect in the function of UDP-glucuronyltransferases, it is planned to study the nature of enzyme-lipid interactions in liver microsomes from Gunn rats in order to clarify further their regulatory significance. Since for many microsomal enzymes it is unclear how many different species of enzymes are needed to account for the catalysis of homologous series of reactions and work in this laboratory suggests that phospholipid-protein interactions may be determinants of the substrate specificity of membrane-bound enzymes, the number of substrate specific forms of UDP-glucuronyltransferase, and the chemical basis for these forms, will be delineated. Finally, our studies of phospholipid-protein interactions will be extended to microsomal acyl-CoA transacylases and UDP-galactosyltransferase.